The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo

Posted by rob on August 28, 2009 under Uncategorized | Comments are off for this article

Dasatinib is an oral potent adenosine triphosphate (ATP)–competitive inhibitor of BCR-ABL, cKIT, platelet-derived growth factor receptor, and SRC family kinases (SFKs), which has demonstrated high efficiency in patients with imatinib-resistant chronic myelogenous leukemia. Here, we show that dasatinib weakly affects platelet activation by thrombin or adenosine diphosphate but is a potent inhibitor of platelet signaling and functions initiated by collagen or FcRIIA cross-linking, which require immunoreceptor tyrosine-based activation motif phosphorylation by SFKs. Accordingly, dasatinib treatment rapidly decreases the volume of thrombi formed under arterial flow conditions in whole blood from patients or mice perfused over a matrix of collagen. Moreover, treatment of mice with dasatin…
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